cissplicing

Cis-splicing is the process by which introns are removed and neighboring exons are joined within a single pre-mRNA molecule to produce mature mRNA. It is the predominant mode of RNA splicing in eukaryotic nuclei and is carried out mainly by the spliceosome, a large dynamic complex composed of small nuclear RNAs and proteins. In canonical cis-splicing, introns typically begin with a GU dinucleotide at the 5' splice site and end with an AG at the 3' splice site. The splicing reaction involves a lariat intermediate formed at a conserved branch point, followed by two transesterification steps that join the flanking exons and release the intron as a lariat structure.

Two major flavors are recognized: spliceosome-mediated cis-splicing of nuclear pre-mRNAs and self-splicing cis-splicing by group II introns, which can catalyze their own removal in some organisms. While group II introns are rare in humans, spliceosome-mediated cis-splicing is universal across metazoans and plants. In addition, a minority of introns, known as U12-type introns, are spliced by a minor spliceosome with distinct recognition motifs.

Alternative cis-splicing events, such as exon skipping or mutually exclusive exons, generate multiple mRNA isoforms from a single gene and contribute to proteomic diversity. Regulation depends on splicing factors (such as SR proteins and hnRNPs), RNA sequence elements, and cellular context, including development and stress. Mis-splicing can lead to disease, including hematologic disorders and neurodegenerative conditions.

Compared with trans-splicing, which joins exons from separate RNA transcripts, cis-splicing occurs within one pre-mRNA and is far more common in higher eukaryotes. Detection and study rely on RNA sequencing, RT-PCR, and intron-exon mapping.